Inflammatory bowel disease (IBD) is of unknown etiology, although immunological mechanisms play a significant role. The two major disorders involved are ulcerative colitis and Crohn's disease. Both diseases are chronic relapsing disorders.
The exact pathogenesis of IBD is unknown. Various factors such as environmental, genetic, smoking and infectious agents have been suggested.
IBD is characterized by a chronic remitting and relapsing course. The general aims of treatment are to induce remission and prevent relapse. The approach to therapy varies according to type, distribution and severity of disease in individual patients.
Current therapies for IBD include anti-inflammatories and steroids and sulphasalazine. Immunosuppressive agents such as azathioprine, 6-mercaptopurine, cyclosporin and methotrexate are emerging as potentially useful agents in severe and refractory cases of IBD. Other treatment modalities undergoing investigation include lipoxygenase inhibitors, fish oil and hydroxychloroquinine.
Exacerbation of inflammatory bowel disease, ulcerative colitis and Crohn's disease, is marked by local release of proinflammatory mediators, increased vascular permeability, and recruitment of acute inflammatory cells, which ultimately leads to mucosal ulceration. It has been shown that proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) tend to be consistently elevated in patients with active IBD. Furthermore, increased levels of angiogenic cytokines such as vascular endothelial growth factor (VEGF) has been recently demonstrated in patients with IBD. Peripheral monocytes and intestinal macrophages from patients with IBD have been found with an enhanced ability to secrete increased amounts of proinflammatory cytokines. An increased capacity to secrete IL-1β and TNF-α, two proinflammatory cytokines particularly important for inducing and sustaining intestinal inflammation in IBD, has been found in polymorphonuclear neutrophil granulocytes (PMN) from patients with active IBD. Reactive oxygen species and nitric oxide mainly released from PMN in patients with IBD have been considered as important factors in the pathogenesis of IBD. It is now becoming clear that inflammatory cells and monocyte- and PMN-released mediators may play a key role in the amplification of inflammation and tissue damage in IBD.
Lipopolysaccharide (LPS) or endotoxin comprises the key element of most gram-negative and some gram-positive bacteria. LPS is an important mediator of gram-negative sepsis and septic shock. LPS itself has been implicated as one of the potent. inducers of proinflammatory mediator synthesis and release, including cytokines and reactive oxygen metabolites in inflammatory cells. Endotoxemia may occur in the absence of gram-negative bacteremia because endotoxin can transit the normal gut wall in small amounts. Such transiting of endotoxin is potentially increased by the presence of mucosal inflammation in patients with active IBD, which eventually leads to endotoxemia.